Pseudomonas aeruginosa is an environmentally-ubiquitous organism which causes opportunistic infections in humans, with a predisposition towards chronically infecting the cystic fibrosis lung. Its high phenotypic and genotypic plasticity facilitates long-term survival, and chronic P. aeruginosa respiratory infections are associated with increased morbidity and mortality. Understanding the drivers and mechanisms of P. aeruginosa adaptation in relation to disease progression is critical for the development of novel detection methods and treatment strategies.

This thesis studies the phenotypic and genotypic adaptation of P. aeruginosa isolates from CF patients, exploring how bacterial characteristics relate to infection stage and severity. By performing whole genome sequence analysis of ten isolates from diverse CF infection backgrounds, common genetic adaptations are identified which occur regardless of infection stage, and analysis of non-coding sequence mutation rate upstream of quorum sensing-regulated genes suggests that certain intragenic sequences may be selectively mutated. This work also investigates whether acute pulmonary exacerbation (or treatment thereof) drives behavioural adaptation of P. aeruginosa, and whether P. aeruginosa phenotypes during these acute periods of infection are similar between patients.

Additionally, this work explores the value and implications of detecting P. aeruginosa quorum sensing molecules in respiratory samples. A DNA-encoded biosensor system is optimised for the detection of the P. aeruginosa quorum sensing molecule 3-oxododecanoyl-homoserine lactone (3OC12-HSL) in CF sputum, and an inverse correlation between sputum 3OC12-HSL levels and P. aeruginosa isolate antibiotic resistance is identified. We also report a correlation between quorum sensing and cyclic-di-GMP signalling, relating this to the regulation of biofilm formation and the acute-to-chronic lifestyle switch.

Overall, this thesis investigates certain P. aeruginosa lifestyles and adaptations in the context of CF respiratory infection, with a particular focus on the use of quorum sensing signalling – both by the bacterium as a mechanism of lifestyle adjustment, and by us for the monitoring of infections.